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Abstract Background Stigma and discrimination towards people with mental health conditions by their communities are common worldwide. This can result in a range of negative outcomes for affected persons, including poor access to health care. However, evidence is still patchy from low- and middle-income countries (LMICs) on affordable, community-based interventions to reduce mental health-related stigma and to improve access to mental health care. Methods This study aims to conduct a feasibility (proof-of-principle) pilot study that involves developing, implementing and evaluating a community-based, multi-component, awareness-raising intervention (titled Indigo-Local), designed to reduce stigma and discrimination and to increase referrals of people with mental health conditions for assessment and treatment. It is being piloted in seven sites in five LMICs—China, Ethiopia, India, Nepal and Tunisia—and includes several key components: a stakeholder group workshop; a stepped training programme (using a ‘Training of Trainers’ approach) of community health workers (or similar cadres of workers) and service users that includes repeated supervision and booster sessions; community engagement activities; and a media campaign. Social contact and service user involvement are instrumental to all components. The intervention is being evaluated through a mixed-methods pre-post study design that involves quantitative assessment of stigma outcomes measuring knowledge, attitudes and (discriminatory) behaviour; quantitative evaluation of mental health service utilization rates (optional, where feasible in sites); qualitative exploration of the potential effectiveness and impact of the Indigo-Local intervention; a process evaluation; implementation evaluation; and an evaluation of implementation costs. Discussion The output of this study will be a contextually adapted, evidence-based intervention to reduce mental health-related stigma in local communities in five LMICs to achieve improved access to healthcare. We will have replicable models of how to involve people with lived experience as an integral part of the intervention and will produce knowledge of how intervention content and implementation strategies vary across settings. The intervention and its delivery will be refined to be feasible and ready for larger-scale implementation and evaluation. This study thereby has the potential to make an important contribution to the evidence base on what works to reduce mental health-related stigma and discrimination and improve access to health care.

This study introduces an alternate spatial-temporal modeling-assisted InSAR time-series analysis method for mine subsidence mapping, aiming to address the large deformation gradients and decorrelation issues. The approach employs the iterative Modeling-Assisted Phase Unwrapping (MA-PU) algorithm for spatial phase unwrapping, and integrates it with temporal models to derive the deformation time-series. Four different inversion procedures are implemented to derive the time-series based on pixel types. The MA-PU method’s effectiveness in handling phase gradients is validated with simulations and real data analysis, showing superiority over non-model-based methods. The incorporation with temporal modeling and time-series inversion demonstrates advantages over time-series inversion alone in dealing with rank-deficiency issues within subsidence zones. The approach is applied to the West Cliff Colliery, Australia, using 23 ALOS-1 data. Results have been compared with GNSS data for validation. Obtained accuracy is approximately 16 mm, with a correlation of 0.99 between the two measurements, showing generally better performances compared to other methods. The comparison result suggest that this approach provides a more robust solution for monitoring mine subsidence in complex scenarios.

ObjectivesTo accurately predict the risk of ischemic stroke, we established a radiomics model of carotid atherosclerotic plaque-based high-resolution vessel wall magnetic resonance imaging (HR-VWMRI) and combined it with clinical indicators.Materials and methodsIn total, 127 patients were finally enrolled and randomly divided into training and test cohorts. HR-VWMRI three-dimensional T1-weighted imaging (T1WI) and contrast-enhanced T1WI (T1CE) were collected. A traditional model was built by recording and calculating radiographic features of the carotid plaques and patients’ clinical indicators. After extracting radiomics features from T1WI and T1CE images, the least absolute shrinkage and selection operator (LASSO) algorithm was used to select the optimal features and construct the radiomics_T1WI model and the radiomics_T1CE model. The traditional and radiomics features were used to build combined models. The performance of all the models predicting ischemic stroke was evaluated in the training and test cohorts, respectively.ResultsBody mass index (BMI) and intraplaque hemorrhage (IPH) were independently related to ischemic stroke and were used to build the traditional model, which achieved an area under the curve (AUC) of 0.79 versus 0.78 in the training and test cohorts, respectively. The AUC value of the radiomics_T1WI model is the lowest in the training and test cohorts, but the prediction performance is significantly improved when the model combines IPH and BMI. The AUC value of the combined_T1WI model was 0.78 and 0.81 in the training and test cohorts, respectively. In addition, in the training and test cohorts, the radiomics_T1CE model based on HR-VWMRI combined clinical characteristics, which is the combined_T1CE model, had the highest AUC value of 0.84 and 0.82, respectively.ConclusionCompared with other models, the radiomics_T1CE model based on HR-VWMRI combined clinical characteristics, which is a combined_T1CE model, can accurately predict the risk of ischemic stroke.

As an upper-middle-income country, China has a vast territory, a large population and substantial variations in the nature of mental health service provision. Guangzhou, one of the five biggest cities in China, is considered as indicative of the current development of mental health services in a more economically developed part of China. In this paper, we first introduce mental health services in Guangzhou and their historical development: from the rising development of mental health care (1949 to the mid-1960s), the stagnant development period of the psychiatric hospitals (1966–1976), the rapid development period of the psychiatric hospitals (1978 to the 1990s), to the integrated development period of community mental health care (2000–2020). This historical trajectory partly reflects the development of mental health services across China. Second, from the public health perspective, we introduce the current mental health care delivery system and resources in Guangzhou, including the psychiatric specialist hospitals, psychiatric units of general hospitals, and community mental health care. Third, based on the current mental health service system, we highlight community mental health care in Guangzhou. We will describe these elements of the mental health system under the following headings: organizational setup, management, and services. We also explore the design of community mental health service models and the challenges in the post-covid-19 era. Finally, we provide considerations and recommendations for mental health service delivery in Guangzhou in the future.

Abstract In view of the problems in traditional geological modeling methods, such as the insufficient utilization of geological survey data, the inaccurate expression of a stratigraphic model, and the large amount of model data, a 3D geological model cannot be smoothly loaded and rendered on the web end. In this paper, a 3D geological implicit modeling method of regular voxel splitting based on hierarchical interpolation data is proposed. This method first uses the boreholes and geological section data from a geological survey for data conversion and fusion, compares the applicability of different interpolation algorithms through cross-validation research, and uses the best fitting algorithm to interpolate and encrypt discrete points in the formation. Then, it constructs the regular voxels, designs five different regular voxel split types, and divides the voxels. In addition, the data structure design of the voxel split model is implemented, and the irregular voxel metadata structure is analyzed and displayed through Three.js. Using this method, based on the survey data of an area in Zhengzhou, the global workflow from data processing to model construction and visualization is demonstrated. The experimental results show that the model can integrate multisource hierarchical interpolation data; express different stratum structures accurately and smoothly, and can realize the rendering, spatial query and analysis of the internal information of a geological body in a browser.

Abstract The shells of window pane oyster Placuna placenta are very thin and exhibit excellent optical transparency and mechanical robustness. However, little is known about the biomineralization-related proteins of the shells of P. placenta. In this work, we report the comprehensive transcriptome of the mantle tissue of P. placenta for the first time. The unigenes of the mantle tissue of P. placenta were annotated by using the public databases such as nr, GO, KOG, KEGG, and Pfam. 24,343 unigenes were annotated according to Pfam database, accounting for 21.48% of the total unigenes. We find that half of the annotated unigenes of the mantle tissue of P. placenta are consistent to the annotated unigenes from pacific oyster Crassostrea gigas according to nr database. The unigene sequence analysis from the mantle tissue of P. placenta indicates that 465,392 potential single nucleotide polymorphisms (SNPs) and 62,103 potential indel markers were identified from 60,371 unigenes. 178 unigenes of the mantle tissue of P. placenta are found to be homologous to those reported proteins related to the biomineralization process of molluscan shells, while 18 of them are highly expressed unigenes in the mantle tissue. It is proposed that four unigenes with the highest expression levels in the mantle tissue are very often related to the biomineralization process, while another three unigenes are potentially related to the biomineralization process according to the Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) analysis. In summary, the transcriptome analysis of the mantle tissue of P. Placenta shows the potential biomineralization-related proteins and this work may shed light for the shell formation mechanism of bivalves.

Mulberry leaf protein hydrolysates (HMP), and their in vitro gastrointestinal digests (GHMP), have shown favorable chemical antioxidant activities. The aim of this study is to investigate the potential protective effects of HMP and GHMP against 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative stress in human erythrocytes. The inhibition rate of hemolysis, the reactive oxygen species (ROS) level, the concentration of malondialdehyde (MDA), the reduced glutathione (GSH) and oxidized glutathione (GSSH), and the enzymatic activities of total superoxide dismutase (SOD), catalase (CAT), and cellular glutathione peroxidase (GSH-Px) were evaluated as the biomarkers of oxidative status in human erythrocytes. The results showed that HMP and GHMP effectively inhibit the occurrence of erythrocyte hemolysis in the range of 0.025–1.0 mg/mL, and the inhibition rates of HMP and GHMP reached 92% and 90% at concentrations of 0.4 mg/mL and 1.0 mg/mL, respectively. HMP and GHMP reduced the AAPH-induced oxidative hemolysis damage via suppressing the generation of ROS by inhibiting the formation of MDA, maintaining the balance of GSH/GSSG, and preserving the activities of the antioxidant enzymes, including SOD, GSH-Px, and CAT. Our findings revealed that both HMP and GHMP could be used as natural antioxidants, and have the potential for further application in the development of functional foods.

Low-molecular-weight organic acids (LMWOAs) that have a wide variety of biological activities can affect the mobilization of heavy metals in soil. In this study, the effects of three kinds of LMWOAs on the remobilization of Cd, Cr, Pb, and As were investigated. The results showed that the concentrations of Cr, Pb, and As reached the maximum values at 7 d, and then decreased at 58 d, indicating that the LMWOAs induced the release of these elements from soil. The ability of LMWOAs to affect the mobility of Cr and As followed the order citric acid (1.32 and 2.51mg/L) > malic acid > oxalic acid, while the order for Pb was malic acid (4.49mg/L) > citric acid > oxalic acid. In addition, the sequential extraction indicated that the LMWOAs advanced the reactivation of Pb, Cd, and As, but led to the immobilization of Cr after a long-term reaction.

High temperatures applied in the production of plant-based meat analogs (PBMA) lead to the occurrence of Maillard reactions, in which harmful compounds Nε-(carboxymethyl)lysine (CML), Nε-(carboxyethyl)lysine (CEL) and acrylamide are formed. However, little research has focused on these compounds in PBMA. In this study, the contents of CML, CEL and acrylamide in 15 commercial-sold PBMA were determined by an ultra-high performance liquid chromatograph coupled with a triple quadrupole tandem mass spectrometer (UHPLC-QqQ-MS/MS). Nutrients (protein, amino acids, fatty acids and sugars) which are related to the formation of these compounds were also studied. The results showed that CML, CEL and acrylamide contents were in the range of 16.46–47.61 mg/kg, 25.21–86.23 mg/kg and 31.81–186.70 μg/kg, respectively. Proteins account for 24.03–53.18% of PBMA. Except for Met + Cys, which is the limiting amino acid of most PBMA, all other indispensable amino acids met the requirements for adults. Besides, PBMA had more n-6 fatty acids than n-3 fatty acids. A correlation analysis showed that proteins and the profiles of amino acid and fatty acid had little influence on CML but significant influence on CEL and acrylamide. The results of the present study can be used as a reference to produce PBMA with higher amounts of nutrients and lower amounts of CML, CEL and acrylamide.

Stroke is a massive public health problem. The rupture of vulnerable carotid atherosclerotic plaques is the most common cause of acute ischemic stroke (AIS) across the world. Currently, vessel wall high-resolution magnetic resonance imaging (VW-HRMRI) is the most appropriate and cost-effective imaging technique to characterize carotid plaque vulnerability and plays an important role in promoting early diagnosis and guiding aggressive clinical therapy to reduce the risk of plaque rupture and AIS. In recent years, great progress has been made in imaging research on vulnerable carotid plaques. This review summarizes developments in the imaging and hemodynamic characteristics of vulnerable carotid plaques on the basis of VW-HRMRI and four-dimensional (4D) flow MRI, and it discusses the relationship between these characteristics and ischemic stroke. In addition, the applications of artificial intelligence in plaque classification and segmentation are reviewed.

ObjectiveStreptococcus pneumoniae (S.pn) is a common respiratory pathogen and a frequent cause of acute otitis media (AOM) in children. However, little is known about the immunometabolism during AOM. This study was to assess the presence of glucose metabolic reprogramming during AOM and its underlying mechanism affecting inflammatory response and middle ear injury.MethodsThe levels of glycolytic metabolism were evaluated by measuring the expression of glycolysis-related genes and the production of metabolites. HE stain, immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and Western blot were performed to measure the effect of glucose metabolic reprogramming on inflammatory response, pneumococcal clearance, hypoxia-inducible factor 1 alpha (HIF-1α) expression and cytokine secretion during AOM, respectively.ResultsThe analysis of microarray revealed an increase of the expression of glycolysis-related genes during S.pn–induced AOM, which was verified by real-time PCR. Increased glycolysis promoted the production of IL-1β and TNF-α and facilitated the clearance of S.pn by enhancing phagocytosis and killing capability of neutrophils, but also aggravated the middle ear injury. Furthermore, these pathogenic effects could be reversed after glycolytic inhibitor 2DG treatment. Additionally, HIF-1α was observed to involve in glycolytic metabolism during AOM.ConclusionS.pn infection induced increased glycolysis conversion during AOM, which promoted inflammatory responses and bacterial clearance, but also aggravated tissue damage.

Neuropathic pain is often closely associated with nerve injury or inflammation, and the role of traditional nonsteroidal anti-inflammatory drugs as adjuvants for treating chemotherapy-induced peripheral neuropathic pain remains unclear. In this study, the potential synergistic antinociceptive effects of indomethacin–pregabalin and meloxicam–pregabalin were evaluated in paclitaxel-induced neuropathic pain and carrageenan-induced inflammatory pain in rodents. Although indomethacin and meloxicam alone only slightly relieved mechanical allodynia in the above two models, isobolographic analysis showed that the combination of indomethacin or meloxicam with pregabalin produced significant synergistic antinociceptive effects for paclitaxel-induced neuropathic pain (IN-PGB, experimental ED25 = [4.41 (3.13–5.82)] mg/kg, theoretical ED25 = [8.50 (6.62–10.32)] mg/kg; MEL-PGB, experimental ED25 = [3.96 (2.62–5.46)] mg/kg, theoretical ED25 = [7.52 (5.73–9.39)] mg/kg). In addition, MEL-PGB dosed via intraplantar injection into the left paw, intragastric injection, or intraperitoneal injection reversed paclitaxel-induced allodynia, indicating that they may act at multiple sites in the neuroaxis and periphery. However, indomethacin–pregabalin and meloxicam–pregabalin exerted antagonistic antiallodynic interactions in carrageenan-induced inflammatory pain in rats. Taken together, coadministration of indomethacin or meloxicam with pregabalin may possess potential therapeutic advantages for treating chemotherapy-induced neuropathic pain.

Olanzapine is a commonly used drug in the treatment of schizophrenia, but its clinical application has been restricted by metabolic-related side effects. In order to mitigate the weight gain side effects caused by olanzapine, other drugs with different targets were selected for combined use and evaluated in animal models of schizophrenia. SEP-363856 is a novel psychotropic agent which is under phase III clinical trials for schizophrenia treatment. The aim of the research was to evaluate whether co-administration of olanzapine and SEP-363856 exerts synergistic anti-schizophrenic effects in the apomorphine (APO)-induced climbing test, the MK-801-induced hyperactivity test, and the Morris water maze test, and therefore reduces the weight gain side effects induced by olanzapine. Through isobolographic analysis, the results showed a synergistic interaction in the climbing test; the experimental ED30 (3 mg/kg) was significantly smaller (p < 0.05) than the theoretical ED30 (5 mg/kg). Additionally, such potentiating effects appeared additive in the MK-801 challenge experiment. Co-treatment with an effective dose of olanzapine and a low dose of SEP-363856 reversed MK-801-induced cognitive impairment symptoms in mice. Moreover, combination treatment with olanzapine and SEP-363856 controls sustained weight gain in mice with chronic exposure to olanzapine. These results support further clinical trials to test the effectiveness of co-treatment of olanzapine and SEP-363856 for controlling symptoms and weight gain in patients with schizophrenia during antipsychotic treatments.

As an important and fundamental step in 3D reconstruction, point cloud registration aims to find rigid transformations that register two point sets. The major challenge in point cloud registration techniques is finding correct correspondences in the scenes that may contain many repetitive structures and noise. This paper is primarily concerned with improving registration using a priori semantic information in the search for correspondences. In particular, we present a new point cloud registration pipeline for large, outdoor scenes that takes advantage of semantic segmentation. Our method consisted of extracting semantic segments from point clouds using an efficient deep neural network, then detecting the key points of the point cloud and using a feature descriptor to get the initial correspondence set, and, finally, applying a Random Sample Consensus (RANSAC) strategy to estimate the transformations that align segments with the same labels. Instead of using all points to estimate a global alignment, our method aligned two point clouds using transformations calculated by each segment with the highest inlier ratio. We evaluated our method on the publicly available Whu-TLS registration data set. These experiments demonstrate how a priori semantic information improves registration in terms of precision and speed.

Gamma-oryzanol (Orz), a mixture of ferulic acid esters of plant sterols and triterpene alcohols, has been proven to possess multiple activities. The purpose of this study was to explore the hepatoprotective effects and potential mechanisms of Orz against ethanol-induced liver injury in mice. Orz pretreatment significantly reduced the serum levels of ALP, ALT, AST and CYP2E1, and increased the TP and GLB levels in the ethanol-challenged mice. Orz increased the activities of CAT, SOD, GSH-PX and the GSH content in the liver, while decreased hepatic steatosis in ethanol-induced liver injure. Furthermore, Orz significantly decreased the protein expression of ASK1, JNK, P38, active-caspase-9 and active-caspase-3, and the protein ratio of Bax/Bcl-2 in livers of ethanol-challenged mice. These results suggest that Orz provides protection against ethanol-induced liver injury which might be due to its alleviation of oxidative stress and inhibition of apoptosis, possibly inhibiting MAPK signaling pathways mediated mitochondrial signaling pathway activation.

The penetration process of rod projectile into concrete target is very complex, and the theoretical analysis is very difficult. In this paper, by using the engineering approximation method, through some reasonable simplification of the rod projectile penetration model, the analytical formulas of the penetration resistance, penetration depth and other important physical quantities are established. Through the calculation of penetration depth, when the sliding friction coefficient is 0.1, the results are in good agreement with the experimental results. The results show that the higher the projectile density and the sharper the shape of the warhead, the stronger the penetration ability.

The calculation of suspension bridge under vertical load is the most important content of suspension bridge design calculation and the most important basis of main component design. Combined with the knowledge of structural mechanics, this paper puts forward the elastic foundation beam algorithm, and deduces the important formulas for the cross-section design and strength comparison of sling, cable and stiffening beam. In use, as long as the parameters are brought into the formula, it is more convenient and fast compared with the complex software modeling. The method proposed in this paper is used to check the strength of the completed Japanese Guanmen bridge, and the results are accurate enough. It is fast and reliable to use this method in the preliminary design and rapid safety assessment of suspension bridge.

Investigation on the formation mechanism of crystals via amorphous precursors has attracted a lot of interests in the last years. The formation mechanism of thermodynamically meta-stable vaterite in pure alcohols in the absence of any additive is less known. Herein, the crystallization process of vaterite microdisc mesocrystals via proto-vaterite amorphous calcium carbonate (ACC) in isopropanol was tracked by using Ca K-edge X-ray absorption spectroscopy (XAS) characterization under cryo-condition. Ca K-edge X-ray absorption near edge structure (XANES) spectra show that the absorption edges of the Ca ions of the vaterite samples with different crystallization times shift to lower photoelectron energy while increasing the crystallization times from 0.5 to 20 d, indicating the increase of crystallinity degree of calcium carbonate. Ca K-edge extended X-ray absorption fine structure (EXAFS) spectra exhibit that the coordination number of the nearest neighbor atom O around Ca increases slowly with the increase of crystallization time and tends to be stable as 4.3 (±1.4). Crystallization time dependent XANES and EXAFS analyses indicate that short-range ordered structure in proto-vaterite ACC gradually transform to long-range ordered structure in vaterite microdisc mesocrystals via a non-classical crystallization mechanism.

Acute otitis media (AOM) is one of the most common infectious diseases primarily caused by Streptococcus pneumoniae (S.pn) among children. Progranulin (PGRN) is a multifunctional growth factor widely expressed in various tissues and cells. Studies have confirmed that PGRN is involved in the development of a variety of inflammatory diseases. We found that the expression of PGRN increased significantly in the middle ear of wild mice with AOM. However, its physiological functions in AOM still remain unknown. To examine the role of PGRN during AOM, we established an acute otitis media model in both C57BL/6 wild mice and PGRN-deficient (PGRN−/−) mice via transbullar injection with S.pn clinical strain serotype 19F. Interestingly, we observed dual results: on one hand, macrophage recruitment notably increased in PGRN−/− mice compared with WT mice; on the other hand, the overall bacterial clearance was surprisingly dampened in PGRN−/− mice. The enhanced recruitment of macrophages was associated with increased production of chemokine (C-C motif) ligand 2 (CCL2), while the decreased bacterial clearance was associated with impaired endocytosis capacity of macrophages. The scavenging ability of bacteria in PGRN−/− mice was recovered with administration of recombinant PGRN. These results suggested a novel dual role of PGRN in affecting the activities of macrophages.

The traditional classroom teaching of mechanics of materials focuses on the theoretical derivation of the formula, and the content is relatively boring. However, in the experimental class, the calculation formula of bending normal stress is simply verified, and other information other than deformation can not be given directly. In order to improve the effect of classroom teaching, ANSYS finite element analysis and pure bending experiment are combined and applied to the classroom teaching of material mechanics. The deformation and stress in the deformation problem of material mechanics are vividly displayed in the form of animation and cloud chart. Practice has proved that this teaching method can not only deepen students’ understanding of abstract mechanical concepts, but also stimulate students’ interest in learning and innovative thinking, which is conducive to the cultivation of engineering application-oriented talents.